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The “Gateway” Allows Cancer Cells to Spread to Blood Vessels

Recently, scientists used real-time, high-resolution imaging technology to determine a a “gateway” in the vasculature, allowing cancer cells to spread from the breast to other parts of the body. These findings provide a better support to predict “whether breast cancer cells will spread,” and this test may help patients avoid from the invasive and unnecessary treatment, as well as bring new cancer therapies.

The study was designated by the US National Cancer Institute, and completed by researchers from the Albert Einstein Cancer Center (AECC) and Montefiore Einstein Center for Cancer Care. They used a mouse model and mice implanted with human breast tissue. Research results were published on August 12 in Cancer Discovery.

Einstein-Montefiore Center for Cancer Care researchers previously found that when directly contacting with three special cells, breast cancer will spread. These three cells are: endothelial cells (a cell lining of blood vessels), perivascular macrophages (nearby blood vessels found in immune cells), and tumor cells which produce high levels of Mena (a protein that can increase the ability of cancer cells invasion). These three cells are direct and stable contact portion – called Tumor Microenvironment of Metastasis(TMEM), which is the site of the tumor cells into the blood vessels.

First author Allison Harney said that, for some time, we already know that tumor vasculature is abnormal with increased permeability, however, we did not know what regulates this permeability; according to our latest imaging research, we can now say that this phenomenon is caused by TMEM macrophages regulation.

The new study suggests that, TMEM macrophages release a protein called vascular endothelial growth factor (VEGF), which causes local vascular permeability increases. This effect is temporary, but could last long enough time, so that the cancer cells enter into the bloodstream- to escape the primary tumor and spread to distant sites of metastases.

Researchers also observed for the first time that transient vascular permeability and tumor cell intravasation occur simultaneously only in TMEM site. They found this phenomenon by intravital high-resolution two-photon microscopy, mirrored humans and mice xenografts (human breast cancer transplanted into mice) of primary breast tumors. These data provide insight into the mechanism of tumor cell intravasation and vascular permeability in breast cancer, explaining the value of TMEM density as a predictor of distant metastatic recurrence in patients.